This application requests funding to acquire a Q-TOF mass spectrometer to replace the mass spectrometer component of an 18-year-old Bruker Esquire-LC/MS system, which is an essential part of the Shared Instrument Facility in the Department of Pharmaceutical Sciences at the University of Tennessee Health Science Center (UTHSC). The Bruker Esquire-LC/MS system has been well maintained and is the work horse supporting extensive small-molecular drug discovery and drug delivery programs at UTHSC in the areas of cancer, obesity, diabetes, radiation protection, radiation mitigation, bacteria inflection, and inflammation diseases. Several small-molecule drug candidates have been licensed for commercial development, including one currently in Phase III clinical trials. However, the age of the current mass spectrometer has resulted in more and more frequent breakdowns in recent years. Bruker officially stopped technical support for this type of instrument system in early 2010. Repair parts are scarce and have become very expensive. The proposed new Q-TOF mass spectrometer will replace the now unreliable mass spectrometer component of the Bruker Esquire-LC/MS system. This powerful new mass spectrometer will benefit more than 10 principal investigators supported by nine R01s, one RC2, one R33, three R21s, and other sources of support. The Q-TOF mass spectrometer will provide years of reliable accessibility, greater sensitivity in both MS and MS/MS modes, and the capability to obtain accurate mass for more efficient structure elucidation. This state-of-the-art instrument wil support drug discovery in preclinical development by using novel small molecules and their translation to innovative therapies for a variety of diseases. UTHSC is strongly committed to supporting biomedical research. The College of Pharmacy will provide $25,000 as a cost share for the purchase of the new instrument, fully support a staff scientist to maintain the Shared Instrument Facility, and assume all future maintenance and repair cost after the warranty period without charging user fees. An advisory committee will ensure effective utilization of the instrument and adequate access by the major users, other NIH-supported investigators, new investigators, and investigators with early-stage projects. PUBLIC HEALTH RELEVANCE: The Q-TOF mass spectrometer requested will replace a technologically limited Esquire-LC/MS mass spectrometer that is nearly two decades old and will provide reliable and sophisticated support for 20 currently funded projects important to human health. These projects focus on small-molecule drug discovery and drug delivery in the areas of cancer, obesity, diabetes, radiation protection, radiation mitigation, bacteria inflection and inflammation diseases.